The Unpaid Debt of Science to Medicine

Prof Timothy Cox used the location of the EWGGD
meeting in the Czech Republic to highlight his opening lecture (summarised
below) on European scientific thought that had developed in Europe since the
years of the Enlightenment in the 17th - 18th Century when the basic conviction
was that through reason mankind could find knowledge and happiness.

Born in Moravia (now the Czech Republic) in 1592, Jan Comenius
was one of the founding fathers of education and science in central and many
parts of Europe. As a result of his influence, the spirit of enquiry in
education was fostered and this tradition enriched the early life and genius of
the monk Gregor Mendel who discovered modern genetics. He later became
Abbott of the Augustinian monastery in Brno which lies about 120 miles east of
Prague.

Mendel observed the inheritance of different characteristics in garden
peas and other plants and carried out ambitious experiments over a period of
eight years. He produced one brilliant paper in 1865-6 whose content was
tragically ignored for almost 50 years but his discoveries provided evidence of
the hereditary material (now known to be DNA) on which evolutionary selection
operates.

Mendel's personal copies of Charles Darwin's Origin of
Species have been discovered; they contain his annotations of Darwin's text
and he must have secretly realised the great significance of his own work.
Element of a Happy Guess Science is knowledge which has to be logically
connected, predictive and testable but there is always an element of a happy
guess at the start. Gauchers disease is an example of how the application of
science has led to therapeutic discovery.

Although the condition is rare, there are sufficient numbers of patients
to render pharmaceutical research worthwhile from the commercial aspect.

Participation of Patients

Many medical investigators have documented the disease's clinical,
pathological, biochemical and genetic features and this has provided the
foundation for drug design and for clear documentation of the effects of
therapy.

All this clinical research has been based on the study of patients
directly. Were it not for the thorough characterisation of Gauchers disease and
the willing participation of patients in clinical trials, the salutary effects
of therapy would not have been so clearly shown.

Orphan drug legislation, introduced in recognition of unmet needs in
society, was an additional powerful incentive to therapeutic development.

Little Known Aspects of the Disease

Prof Cox devoted much of his lecture to little known aspects of
Gauchers disease and the mechanism of action of different therapies real and
potential.

He explained that effective treatment depends on a complete
understanding of the disease process itself. It is still not possible to make
the mechanistic connection between the presence of a few grams of storage
material and the complex syndrome termed Gauchers disease and that despite its
effectiveness, neither enzyme replace-ment nor any other therapy actually cures
the condition.

Refinements in existing medicines or the introduction of new strategies,
including gene therapy, are justified for the advancement of Gauchers disease
and related lysosomal diseases and this all required more investment in
fundamental research.

There are other puzzles too: it is recognized that unknown
environ-mental factors may operate to explain why, in the case of two identical
twin sisters having the same glucocere-brosidase gene mutations and with the
same complement of DNA, only one developed symptoms and needed a splenectomy
whilst the other twin remained healthy.

The nature of the gene-environment interactions that induce or
exacerbate clinical disease perhaps remains even more of a mystery. A
completely novel experimental approach is going to be needed to understand
these interactions in human medicine.

Just as Medicine depends on continuing scientific development and
experimental work, Science too owes a huge debt to Medicine. The European
Working Group on Gaucher Disease clearly had plenty of research opportunities
in to the disease.